Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D473/00—Heterocyclic compounds containing purine ring systems
  • C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
  • C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
  • C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
  • C07D473/08—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3 with methyl radicals in positions 1 and 3, e.g. theophylline

Definitions

• A is hydroxyl, or a carboxyl containing group g m or a halogenide, acid anhydride or ester thereof, with v a compound of the formula.
• R is lower alkyl containing from I to 5 carbon ing effects and is, therefore, effective in the treatment of angina pectoris. However, it also stimulates the heart rate and enhances myocardial oxygen consumption, which results in an insufficient supply of oxygen to the heart.
• one object of this invention is to provide theophylline derivatives having the formula (I) which possess superior coronary vasodilating effects.
• Another object of this invention is to provide an industrially advantageous process for the synthesis of theophylline derivatives represented by formula (I).
• Suitable functional groups for the group A include hydroxyl, or carboxyl containing groups of halogenides, acid anhydrides or esters thereof.
• Suitable functional groups for the group B include hydrogen, hydroxyl, carboxyl containing groups or halogenides, acid anhydrides or esters thereof.
• Suitable R groups in compound I" include methyl, ethyl, propyl, isopropyl and the like.
• theophylline compounds of this in vention exhibit excellent coronary vasodilating effects while at the same time exhibiting lesser adverse effects on the myocardium in comparison to theophylline.
• EXAMPLE l 7-[-y-( 3 ,4,5-Trimethoxybenzyloxy)-n-propyl theophylline A 5.2 g (0.023 moles) quantity of 3,4,5- trimethoxybenzoyl chloride, 4.8 g (0.02 moles) of 7-(yhydroxy-n-propyl) theophylline and 4.0 g (0.04 moles) of triethylamine were dissolved in ISO ml of anhydrous benzene. The resulting solution was refluxed for 8 hours.
• EXAMPLE 2 7-['y-( 3,4,5-Trimethoxyphenoxycarbonyl)-npropyl]theophylline
• An 8.0 g (0.03 moles) amount of 7-(y-carboxy-npropyl)-theophylline, 5.5 g (0.03 moles) of 3,4,5- trimethoxyphenol and 0.03 moles of phosphorus oxychloride were dissolved in 200 mol of anhydrous benzene. The resulting solution was refluxed for hours. After cooling, the reaction mixture was washed with a saturated sodium bicarbonate solution and a saturated saline solution. The washed solution was dried over anhydrous sodium sulfate and the solvent was evaporated therefrom. By this procedure was obtained 9.2 g of a white crystalline material. Recrystallization of the material from benzene afforded 8.5 g (66% of yield) of a white crystalline product having a metling point of 154-l56C.
• EXAMPLE 3 7-['y-(2,3,4-Trimethoxybenzoyl )-n-propyl]- theophylline An g (0.03 moles) amount of 7-(y-carboxy-npropyl)-theophylline and 3.3 g (0.02 moles) of I23- trimethoxybenzene were dissolved in 12.6 g (0.06 moles) of trifluoroacetic anhydride. The resulting solution was refluxed for 2.5 hours. After cooling, sodium bicarbonate was added to the reaction mixture in a quantity which gave a final pH of 7.0. After extracting the solution with benzene.
• the extract obtained was washed with a saturated sodium bicarbonate solution and a saturated saline solution.
• the washed solution was dried over anhydrous sodium sulfate and the solvent was evaporated therefrom.
• An 8.9 g amount of a reddish oily substance was obtained.
• This oily substance was recrystallized from isopropyl ether and further recrystallization from benzene-isopropyl ether afforded 5.l g (41% of yield) of pale yellow needles of a compound having a melting point of l l9-l 20C.

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Citations (2)

• 1972
  • 1972-07-13 JP JP47070294A patent/JPS5132638B2/ja not_active Expired
• 1973
  • 1973-07-02 GB GB3149873A patent/GB1384855A/en not_active Expired
  • 1973-07-12 FR FR7325672A patent/FR2192825B1/fr not_active Expired
  • 1973-07-13 CH CH204576A patent/CH580098A5/xx not_active IP Right Cessation
  • 1973-07-13 CH CH1029073A patent/CH575948A5/xx not_active IP Right Cessation
  • 1973-07-13 DE DE19732335764 patent/DE2335764A1/de active Pending
  • 1973-07-13 US US378806A patent/US3896127A/en not_active Expired - Lifetime

Patent Citations (2)

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